Type1 diabetes risk genes

An interesting diagram…time to get genetic testing done for me and my family. From the book Diabetes in the Genes and Diseases series…author Toney Allman.

So tell me…does this mean a son from a T1 mother is more at risk? If so, how could i get my son tested?

It means that if the HLA genes with DR3 and DR4 variants are both present in the child, then there is higher risk for developing type-1 diabetes. I need to ask my endo about genetic testing as I have no idea how to go about getting this done.

Apparently, if one has DR2 variation in the HLA genes, then there is protection against developing Type 1 and a person with the DR2 variation will never get Type 1 diabetes. The DR3 and DR4 variations make one susceptible to autoimmune disease. 95% of Caucasians with Type 1 have at least one of these variations.

The diagram does not say anything about increased risk from mother.

All of the genetic stuff is complicated. There are many genotypes involved both increasing the risk and being protective (http://diabetes.diabetesjournals.org/content/early/2008/02/05/db07-1331.abstract). I don’t even pretent to understand this. If you are considering the risks in your children it may be worth it to you to evaluate this, but it may or may not provide any clear information on increased or decreased risk. There are certainly combinations that have been found. Researchers have started to collaborate through the T1 Diabetes Genetics Consortium (https://www.t1dgc.org/home.cfm). By sharing data, it is hoped that further progress can be made. The literature in this field is almost a foreign language. Without a background in the terminology and nomenclature it is really hard to understand. The book you cite is probably a good way to get a feel for things.

Hey, I’m curious what the reasons would be for getting the test? If T2 runs in your family, you know what you have to do to keep your risks low and even that won’t completely eliminate the chance. If you’re T1, it’s pretty random. Even if you find out your likelyhood is high, there’s no gaurantee and if you knew %100 that it’s coming, there’s nothing you can do to prevent it, right? Personally, I wouldn’t have wanted to know that I would get this 5 or 10 years before I got it, I would have had 5 or 10 years of constant stress and worry just holding my breath in constant fear that this was it!

Great point Barb,

I am T1 for 25 years. My wife is not. When my son was born, now four, we enrolled him in TRIGR. They took cord blood and had it tested for the “diabetes genes” and it it turns out he has them. I don’t know exactly which variant. What I do know is that because I know he has the genes associated with developing T1, I worry about it constantly. Every cold, virus, request for another sippy cup, trip to the bathroom…you name it I think T1. I wish I didn’t know. Like you said, there’s nothing I can do about it anyway. My daughter, two, is not in the study. I have no idea if she is a carrier or not and I almost never think of it with her.

I would strongly encourage anyone considering genetic testing to think, “Do I really want to know?” If you are like me, I only wanted to know if it was the answer I was hoping for.

I agree Rick…there is enough to worry about with kids. It seems almost masochistic to know that maybe…one day…who knows when…your son might become diabetic. I think you take the approach like he does not have the gene and go on from there. The phrase “ignorance is bliss” was coined for a reason. Who knows…your son may never get it or he could be like me and get it at the ripe old age of 46!!! I pray for the former for you and your son!!!

Let me comment on the other side of this situation. I have type 1 diagnosed a little before my 11th birthday in 1958. However, I am homozygous HLA DR 8 DQ 402 which gives almost the same risk (1.25 times general population risk) of type 1 diabetes as the general population. I do not have any of the hereditary factors mentioned in the chart. In other words, parents like mine whose genotype would indicate no increased risk of type 1 diabetes still may have a child with the disease. Also even people with high risk genes do not always develop type 1 diabetes.

Exactly. There’s no way of knowing for sure but either way, why take on many years of worrying about something you may or may not get and have no control over (T1)! I’m assuming you didn’t know this before diagnosis?

When I was diagnosed HLA typing, antibody testing etc. did not exist; so, there was no way for my parents to even suspect that one of their children would have diabetes. It was in fact, quite a shock to them.

Most diseases that seem to have a hereditary component do not have a simple genetic factor; instead they can be the result of many genetic and environmental factors. For this reason it makes little sense to worry about the genetics that one might be passing to their children.

I agree!

Wow, this is not my understanding. T2 is perhaps genetic and triggered like T1. Dan Hurley in his book “Diabetes Rising” actually explores the idea that T1 and T2 are the same class of disorder, just expressed along different spectrums. How can you reduce your risk of getting T1? I don’t know, perhaps the same way you reduce the risk of T2. I am not sure what I would have done to reduce my risk (as a T2). What should have I done? I was never overweight. The idea that T2s created their condition is my view often a sad confusion of cause and effect.

Point being, there’s no real reason for anyone to need to know.

I’m not sure I’d want to know, honestly. Waiting for that shoe to drop? If there was a semi-guaranteed way to delay or prevent, I’d be all over it. Given the fact I’m the only one in my family with this disease, going back to 3rd cousins, I’m ok betting on my chances. With 3 children, one of them could develop it eventually. Then I’d feel so guilty.

I hate this disease.

I never said they brought it on themselves.

Sorry to misinterpret your comments. My point was that both t1s and t2s may have questions about about how diabetes is inherited. Both t1 and t2 have clearly identified overlapping genetically inherited risk factors.